This invention relates to phosphonic acid compositions for investigations of in vivo deposits of calcium and their use for diagnosis by scanning and for therapy by concentrating sufficient radioactivity in areas of skeletal pathology (metabolic, primary cancers, metastases). Scanning is defined to include emission studies (photon, NMR, X-ray Fluorescence) and transmission studies (convention X-ray, transmission tomography).
At the present time, there are a wide variety of radioactive compositions which, when administered to a human, will accumulate in specific organs, tissues or sketetal material. After administration, radiation detection apparatus are used to visualize the target areas to monitor the function of the organ, tissue or skeletal material.
Presently, there are available a wide variety of phosphorous compounds which have been radiolabeled with technetium in order to produce radiolabeled compounds which are specific to deposition in the skeleton. Exemplary compounds are disclosed, for example, in U.S. Pat. Nos. 3,735,001, 3,931,396, 3,947,268, 3,984,531, 3,989,730, 4,016,249, 4,233,284 and 4,234,502. All of these compounds are labeled with technetium-99m. It is desirable to utilize technetium-99m as a radiolabel since it has high specific activity which makes possible visualization of the entire skeleton, yet the radiation is easily collimated. Technetium-99m also has a relatively rapid rate of decay of about 6 hr half-life which makes it useful for many diagnostic purposes. In addition, the decay product (technetium-99m) has low radiation levels which renders it safe for use in patients. Also, technetium-99m is readily available from molybdenum-99m generators.
While technetium-labeled bone seeking complexes are suitable in scintigraphy, their use is limited to determining the condition of the skeletal structure for only a short period corresponding to the decay characteristics for technetium-99m, usually only for about 6 hr. In many cases, it is desirable to monitor the condition of the skeletal structure for a longer period, so that the long term effects of a particular treatment on or the natural healing rate of a particular portion of the skeletal structure can be monitored over relatively long periods such as 60 days or more.
Prior to the present invention, there has not been available a substrate which, after labeling with a suitable radionuclide, would afford short and long term analysis of skeletal metabolism. Complexes which afford analysis by scanning over short time periods corresponds to the physical decay of technetium-99m and those suitable for long time analysis include complexes labeled with radionuclides with longer physical half-lives. The latter include halogens consisting of iodine-123, iodine-125 and iodine-131.
It would be desirable to provide scanning agents which are highly selective in their affinity for in vivo calcium deposits (such as the skeleton) as compared to other parts of the body. Furthermore, it would be desirable to provide such scanning agents that would permit both short term and long term monitoring of changes in calcium metabolism without harm to the patient. Such scanning agents then would provide a means for comparing changes in calcium metabolism in normal and diseased states.